Pegylated albumin polymers and uses thereof

Abstract

The present invention provides an albumin polymer and a process of making an albumin polymer, the process comprising breaking instrinsic disulfide bridges in albumin with a reducing agent and crosslinking inter- and intra-molecular disulfide bridges so as to form the polymer. The present invention also provides PEGylated albumin polymers and methods of making PEGylated albumin polymers, the methods comprising polymerizing albumin by crosslinking inter- and intra-molecular disulfide bridges, and PEGylating the albumin polymer. The present invention further provides a pharmaceutical composition useful as a blood plasma expander, blood substitute or for drug delivery, and methods of treating blood loss in a subject and of delivering drugs to a subject's tissue, the pharmaceutical composition comprising a therapeutically effective amount of the PEGylated albumin polymer.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims benefit of U.S. Provisional Application No. 61 / 339,020, filed Feb. 25, 2010, the contents of which are hereby incorporated by reference.FIELD OF THE INVENTION[0002]The present invention relates generally to PEGylated albumin polymers and their uses for enhanced plasma expansion and drug delivery.BACKGROUND OF THE INVENTION[0003]Throughout this application various publications are referred to by number in parenthesis. Full citations for these references may be found at the end of the specification. The disclosures of these publications are hereby incorporated by reference in their entirety into the subject application to more fully describe the art to which the subject invention pertains.[0004]Plasma expansion is the initial treatment for blood losses and is a continued treatment in patients with prolonged recovery. Blood loss is associated with conditions such as trauma and surgery. Plasma expansion treatment for b...

AI Technical Summary

Benefits of technology

The present invention provides a method of preparing an albumin polymer by crosslinking inter- and intra-molecular disulfide bridges, as well as a PEGylated albumin polymer. The polymer can be used for blood plasma expander, blood substitute, or drug delivery. The therapeutic effect of the PEGylated albumin polymer is to treat blood loss or deliver drugs to a subject's tissue. The method for preparing the polymer can be easily implemented and the resulting polymer has improved properties compared to natural albumin.

Problems solved by technology

This approach has shown to be a moving target, with uncertain outcome, as academic and industrial efforts continually fail to deliver an oxygen-carrying plasma expander or “blood substitute”(1).

Providing oxygen transport capacity to a plasma expander fails due to problems intrinsic to the oxygen carrier.

The blood viscosity tightly regulates microvascular flow homeostasis and if reduced below a critical level will lead to reduced stimulation and malfunction of the endothelium, causing capillary collapse and reduced tissue perfusion.

However, these colloids can only be used at comparatively low hematocrits (<18%) because a higher concentration leads to red blood cell aggregation.

These products have a short circulation life and cause adverse effects such as red blood cell aggregation and interference with blood coagulation.

However, they are not ideal since PEGylated albumins are associated with high colloid oncotic pressure (COP) in addition to high viscosity (8).

Images